Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
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Query Trace: Duffy D[original query] |
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Characterization of carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa carrying multiple carbapenemase genes-Antimicrobial Resistance Laboratory Network, 2018-2022
Sabour S , Harrington KRV , Martinson E , Bhatnagar AS , Huang JY , Duffy D , Bantle K , Lutgring JD , Karlsson M , Baca S . J Clin Microbiol 2024 e0122024 Carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are significant public health threats, particularly when harboring carbapenemases. Literature describing the frequencies and phenotypic and genotypic characteristics of isolates harboring multiple carbapenemase genes is limited. Using data collected from the Antimicrobial Resistance Laboratory Network (AR Lab Network) in 2018-2022, we describe CRE and CRPA isolates that harbor multiple acquired carbapenemase genes. Clinical laboratories submitted CRE and CRPA isolates to AR Lab Network public health laboratories for additional characterization that included antimicrobial susceptibility testing and detection of five targeted carbapenemase genes. Isolates were classified as non-carbapenemase producing (non-CP) when negative for carbapenemase production and all targeted carbapenemase genes, or positive for a single-CP (SCP) or multiple-carbapenemase (MCP) targeted gene. Among 79,799 CREs tested, 27,599 (35%) were SCP and 611 (1%) were MCP. MCP-CRE most often carried bla(KPC)/bla(NDM) (n = 285, 47%). Both SCP-CRE and MCP-CRE were most commonly Klebsiella spp. Enterobacter spp. and Escherichia coli isolates harboring MCP were detected at slightly higher frequencies (18% and 15%; n = 109 and n = 88, respectively) than Enterobacter spp. and Escherichia coli isolates harboring SCP (13% and 13%; n = 3,653 and 3,471, respectively). The number of MCP-CRE detected increased from 54 of 5,105 (1%) in 2018 to 223 of 6,994 (3%) in 2022. Among 54,490 CRPA tested, 2% (n = 1,249) were SCP and 31 were MCP. MCP-CRPA most often carried bla(VIM)/bla(IMP) (n = 13, 42%). A higher proportion of MCP-CRE (97%, n = 330) isolates were categorized as resistant to meropenem, compared to SCP-CRE (79%; n = 11,227) and non-CP (13%; n = 2,683). Although MCP organisms represent a small proportion of total CP detected in the AR Lab Network, there is a need for continued monitoring and additional research.IMPORTANCECarbapenemase-producing organisms are of significant clinical and public health concerns, and rapid detection and containment of such threats are vital to preventing their spread. In this article, we used a collection of over 130,000 contemporary isolates to evaluate frequencies and phenotypic and genotypic properties of CRE and CRPA isolates harboring multiple carbapenemase genes across the United States, from 2018 to 2022. Of note, 95% and 100% of CRE and CRPA isolates co-harbored at least one metallo-β-lactamase gene, respectively, indicating a high proportion of isolates originating from patients with difficult-to-treat infections. Both clinical and public health professionals across the nation can use these data and key findings to better understand the molecular landscape of these isolates. Timely detection and control of these organisms are essential to combating the spread of antibiotic resistance and ensuring the availability of effective treatment options for patients. |
JYNNEOS vaccine safety surveillance in the vaccine safety datalink during the 2022 mpox outbreak in the United States
Duffy J , Yih WK , Walton K , DeSilva MB , Glanz JM , Hambidge SJ , Jackson LA , Klein NP , Lewin BJ , Naleway AL , Sundaram ME , Maro JC , Weintraub E . Infection 2024 BACKGROUND: The JYNNEOS vaccine (two doses given 28 days apart) was recommended in the United States for people at high risk of exposure to monkeypox virus during the 2022 mpox outbreak. Our objective was to assess the safety of JYNNEOS using two complementary epidemiologic methods. METHODS: This observational cohort included patients of eight large integrated healthcare organizations who received JYNNEOS. Adverse events were identified using ICD-10 coded diagnoses assigned to medical visits. The first analysis used standardized incidence ratios (SIR) to compare the observed incidence of ten prespecified adverse events of special interest (AESI) during the 28 days after receipt of each dose of JYNNEOS to the expected incidence adjusted for several risk factors. The second analysis used tree-based data mining to identify temporal clustering of cases for more than 60,000 diagnoses and diagnosis groups within 70-days after JYNNEOS dose 1 administration. RESULTS: The SIR analysis included 53,583 adults who received JYNNEOS dose 1 and 38,206 who received dose 2. Males received 92% of the doses. There were no statistically significant elevated SIRs for any of the ten AESI. The tree-based data mining analysis included 36,912 vaccinees. Analysis of diagnoses in inpatient, emergency department, and outpatient settings identified statistically significant clusters of visits for rash and unspecified adverse effects. CONCLUSIONS: No new or unexpected safety concerns were identified. AESI did not occur more frequently than expected by chance alone. Non-serious medically attended adverse events, such as rash, have been previously reported and occurred infrequently. |
Safety of simultaneous vs sequential mRNA COVID-19 and inactivated influenza vaccines: A randomized clinical trial
Walter EB , Schlaudecker EP , Talaat KR , Rountree W , Broder KR , Duffy J , Grohskopf LA , Poniewierski MS , Spreng RL , Staat MA , Tekalign R , Museru O , Goel A , Davis GN , Schmader KE . JAMA Netw Open 2024 7 (11) e2443166 IMPORTANCE: Limited randomized clinical trial data exist on the safety of simultaneous administration of COVID-19 and influenza vaccines. OBJECTIVE: To compare the reactogenicity, safety, and changes in health-related quality of life (HRQOL) after simultaneous vs sequential receipt of messenger RNA (mRNA) COVID-19 vaccine and quadrivalent inactivated influenza vaccine (IIV4). DESIGN, SETTING, AND PARTICIPANTS: This randomized, placebo-controlled clinical trial was conducted between October 8, 2021, and June 14, 2023, at 3 US sites. Participants were nonpregnant persons aged 5 years or older with the intention of receiving both influenza and mRNA COVID-19 vaccines. INTERVENTIONS: Intramuscular administration in opposite arms of either IIV4 or saline placebo simultaneously with mRNA COVID-19 vaccine at visit 1. Those who received placebo at visit 1 received IIV4 and those who received IIV4 at visit 1 received placebo 1 to 2 weeks later at visit 2. MAIN OUTCOMES AND MEASURES: The primary composite reactogenicity outcome was the proportion of participants with fever, chills, myalgia, and/or arthralgia of moderate or greater severity within 7 days after vaccination visits 1 and/or 2, using a 10% noninferiority margin. Secondary outcomes were solicited reactogenicity events and unsolicited adverse events (AEs) for 7 days after each visit separately and HRQOL after visit 1, assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index. Serious AEs (SAEs) and AEs of special interest (AESIs) were assessed for 121 days. Outcomes were compared between groups. RESULTS: A total of 335 persons (mean [SD] age, 33.4 [15.1] years) were randomized (169 to the simultaneous group and 166 to the sequential group); 211 (63.0%) were female, and 255 (76.1%) received bivalent BNT162b2 mRNA COVID-19 vaccine. The proportion with the primary composite reactogenicity outcome in the simultaneous group (25.6% [n = 43]) was noninferior to the proportion in the sequential group (31.3% [n = 52]) (site-adjusted difference, -5.6 percentage points [pp]; 95% CI, -15.2 to 4.0 pp). Respective proportions in each group were similar after each visit separately (visit 1, 40 [23.8%] vs 47 [28.3%]; visit 2, 5 [3.0%] vs 9 [5.4%]). No significant group differences in participants with AEs (21 [12.4%] vs 16 [9.6%]), SAEs (1 [0.6%] vs 1 [0.6%]), and AESIs (19 [11.2%] vs 9 [5.4%]) were observed in the simultaneous vs sequential groups, respectively. Among participants with severe reactogenicity, the mean (SD) EQ-5D-5L Index score decreased from 0.92 (0.08) to 0.92 (0.09) prevaccination to 0.81 (0.09) to 0.82 (0.12) postvaccination. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial assessing simultaneous vs sequential administration of mRNA COVID-19 and IIV4 vaccines, reactogenicity was comparable in both groups. These findings support the option of simultaneous administration of these vaccines. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05028361. |
JYNNEOS vaccine safety surveillance during the 2022 mpox outbreak using the Vaccine Adverse Event Reporting System (VAERS) and v-safe, United States, 2022-2023
Duffy J , Myers TR , Marquez P , Rouse D , Brown H , Zhang B , Shay DK , Moro PL . Sex Transm Dis 2024 51 (8) 509-515 BACKGROUND: In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive 2 doses of the JYNNEOS vaccine. Vaccine safety was monitored using 2 complementary systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events after vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns. Medical records were requested and reviewed for adverse events of special interest, including myocarditis. Adverse event reporting rates were calculated as the number of verified adverse event cases divided by the number of JYNNEOS doses administered. V-safe for mpox was a voluntary smartphone-based vaccine safety surveillance system that sent enrolled persons text messages linked to health surveys asking about reactions and health impact events occurring after vaccination. RESULTS: There were 1,207,056 JYNNEOS doses administered in the United States. VAERS received 1927 reports for JYNNEOS. The myocarditis reporting rate per million doses was 2.69 after dose 1 and 8.64 after dose 2. V-safe had 213 participants complete at least one health survey. Rates of injection site and systemic reactions were similar in the first week after dose 1 and dose 2. CONCLUSIONS: JYNNEOS vaccine safety surveillance findings from VAERS and v-safe did not identify any unexpected safety concerns. The VAERS reporting rate for myocarditis was similar to previously published population background rates. |
Tinnitus after COVID-19 vaccination: Findings from the vaccine adverse event reporting system and the vaccine safety datalink
Yih WK , Duffy J , Su JR , Bazel S , Fireman B , Hurley L , Maro JC , Marquez P , Moro P , Nair N , Nelson J , Smith N , Sundaram M , Vasquez-Benitez G , Weintraub E , Xu S , Shimabukuro T . Am J Otolaryngol 2024 45 (6) 104448 PURPOSE: To assess the occurrence of tinnitus following COVID-19 vaccination using data mining and descriptive analyses in two U.S. vaccine safety surveillance systems. METHODS: Reports of tinnitus after COVID-19 vaccination to the Vaccine Adverse Event Reporting System (VAERS) from 2020 through 2024 were examined using empirical Bayesian data mining and by calculating reporting rates. In the Vaccine Safety Datalink (VSD) population, ICD-10 coded post-vaccination medical visits were examined using tree-based data mining, and tinnitus visit incidence rates during post-vaccination days 1-140 were calculated by age group for COVID-19 vaccines and for comparison, influenza vaccine. RESULTS: VAERS data mining did not find disproportionate reporting of tinnitus for any COVID-19 vaccine. VAERS received up to 84.82 tinnitus reports per million COVID-19 vaccine doses administered. VSD tree-based data mining found no signals for tinnitus. VSD tinnitus visit incidence rates after COVID-19 vaccines were similar to those after influenza vaccine except for the group aged ≥65 years (Moderna COVID-19 vaccine, 165 per 10,000 person-years; Pfizer-BioNTech COVID-19 vaccine, 154; influenza vaccine, 135). CONCLUSIONS: Overall, these findings do not support an increased risk of tinnitus following COVID-19 vaccination but cannot definitively exclude the possibility. Descriptive comparisons between COVID-19 and influenza vaccines were limited by lack of adjustment for potential confounding factors. |
FDA, CDC, and NIH Co-sponsored Public Workshop Summary-Development Considerations of Antimicrobial Drugs for the Treatment of Gonorrhea
Hiruy H , Bala S , Byrne JM , Roche KG , Jang SH , Kim P , Nambiar S , Rubin D , Yasinskaya Y , Bachmann LH , Bernstein K , Botgros R , Cammarata S , Chaves RL , Deal CD , Drusano GL , Duffy EM , Eakin AE , Gelone S , Hiltke T , Hook Iii EW , Jerse AE , McNeil CJ , Newman L , O'Brien S , Perry C , Reno HEL , Romaguera RA , Sato J , Unemo M , Wi TEC , Workowski K , O'May GA , Shukla SJ , Farley JJ . Clin Infect Dis 2024 There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop. |
Carbapenem-resistant and extended-spectrum β-Lactamase-producing enterobacterales in children, United States, 2016-2020
Grome HN , Grass JE , Duffy N , Bulens SN , Ansari U , Campbell D , Lutgring JD , Gargis AS , Masters T , Kent AG , McKay SL , Smith G , Wilson LE , Vaeth E , Evenson B , Dumyati G , Tsay R , Phipps E , Flores K , Wilson CD , Czaja CA , Johnston H , Janelle SJ , Lynfield R , O'Malley S , Vagnone PS , Maloney M , Nadle J , Guh AY . Emerg Infect Dis 2024 30 (6) 1104-1114 |
Effectiveness of recombinant zoster vaccine against herpes zoster in a real-world setting
Zerbo O , Bartlett J , Fireman B , Lewis N , Goddard K , Dooling K , Duffy J , Glanz J , Naleway A , Donahue JG , Klein NP . Ann Intern Med 2024 BACKGROUND: A 2-dose series of recombinant zoster vaccine (RZV) was 97% effective against herpes zoster (HZ) in a pivotal clinical trial. OBJECTIVE: To evaluate real-world effectiveness of RZV against HZ. DESIGN: Prospective cohort study. SETTING: Four health care systems in the Vaccine Safety Datalink. PARTICIPANTS: Persons aged 50 years or older. MEASUREMENTS: The outcome was incident HZ defined by a diagnosis with an antiviral prescription. Cox regression was used to estimate the hazard of HZ in vaccinated persons compared with unvaccinated persons, with adjustment for covariates. Vaccine effectiveness (VE) was calculated as 1 minus the adjusted hazard ratio and was estimated by time since the last RZV dose and by corticosteroid use. RESULTS: The study included nearly 2.0 million persons who contributed 7.6 million person-years of follow-up. After adjustment, VE of 1 dose was 64% and VE of 2 doses was 76%. After 1 dose only, VE was 70% during the first year, 45% during the second year, 48% during the third year, and 52% after the third year. After 2 doses, VE was 79% during the first year, 75% during the second year, and 73% during the third and fourth years. Vaccine effectiveness was 65% in persons who received corticosteroids before vaccination and 77% in those who did not. LIMITATION: Herpes zoster could not be identified as accurately in these observational data as in the previous clinical trials. CONCLUSION: Two doses of RZV were highly effective, although less effective than in the previous clinical trials. Two-dose effectiveness waned very little during the 4 years of follow-up. However, 1-dose effectiveness waned substantially after 1 year, underscoring the importance of the second dose. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention. |
Trends in incidence of carbapenem-resistant enterobacterales in 7 US sites, 2016─2020
Duffy N , Li R , Czaja CA , Johnston H , Janelle SJ , Jacob JT , Smith G , Wilson LE , Vaeth E , Lynfield R , O'Malley S , Vagnone PS , Dumyati G , Tsay R , Bulens SN , Grass JE , Pierce R , Cassidy PM , Hertzel H , Wilson C , Muleta D , Taylor J , Guh AY . Open Forum Infect Dis 2023 10 (12) ofad609 BACKGROUND: We described changes in 2016─2020 carbapenem-resistant Enterobacterales (CRE) incidence rates in 7 US sites that conduct population-based CRE surveillance. METHODS: An incident CRE case was defined as the first isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to ≥1 carbapenem from a sterile site or urine in a surveillance area resident in a 30-day period. We reviewed medical records and classified cases as hospital-onset (HO), healthcare-associated community-onset (HACO), or community-associated (CA) CRE based on healthcare exposures and location of disease onset. We calculated incidence rates using census data. We used Poisson mixed effects regression models to perform 2016─2020 trend analyses, adjusting for sex, race/ethnicity, and age. We compared adjusted incidence rates between 2016 and subsequent years using incidence rate ratios (RRs) and 95% confidence intervals (CIs). RESULTS: Of 4996 CRE cases, 62% were HACO, 21% CA, and 14% HO. The crude CRE incidence rate per 100 000 was 7.51 in 2016 and 6.08 in 2020 and was highest for HACO, followed by CA and HO. From 2016 to 2020, the adjusted overall CRE incidence rate decreased by 24% (RR, 0.76 [95% CI, .70-.83]). Significant decreases in incidence rates in 2020 were seen for HACO (RR, 0.75 [95% CI, .67-.84]) and CA (0.75 [.61-.92]) but not for HO CRE. CONCLUSIONS: Adjusted CRE incidence rates declined from 2016 to 2020, but changes over time varied by epidemiologic class. Continued surveillance and effective control strategies are needed to prevent CRE in all settings. |
Impact of the COVID-19 pandemic on health care utilization in the vaccine safety datalink: Retrospective cohort study
Qian L , Sy LS , Hong V , Glenn SC , Ryan DS , Nelson JC , Hambidge SJ , Crane B , Zerbo O , DeSilva MB , Glanz JM , Donahue JG , Liles E , Duffy J , Xu S . JMIR Public Health Surveill 2023 BACKGROUND: Understanding the long-term impact of the COVID-19 pandemic on health care utilization is important to health care organizations and policy makers for strategic planning, as well as to researchers when designing studies that use observational electronic health record data during the pandemic period. OBJECTIVE: To evaluate changes in health care utilization across all care settings among a large diverse insured population in the United States during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort study within 8 health care organizations participating in the Vaccine Safety Datalink Project using electronic health record data from members of all ages during January 1, 2017 - December 31, 2021. The visit rates per person-year were calculated monthly during the study period for four health care settings combined as well as by inpatient, emergency department (ED), outpatient, and telehealth settings, both among all members and members without COVID-19. Difference-in-difference analysis and interrupted time series analysis were performed to assess the changes in visit rates from the pre-pandemic period (January 2017 to February 2020) to the early pandemic period (April 2020 to December 2020) and the later pandemic period (July 2021 to December 2021), respectively. An exploratory analysis was also conducted to assess trends through June 2023 at one of the largest sites, Kaiser Permanente Southern California (KPSC). RESULTS: The study included more than 11 million members from 2017 to 2021. Compared with the pre-pandemic period, we found reductions in visit rates during the early pandemic period for all in-person care settings. During the later pandemic period, overall utilization reached 8.36 visits per person-year, exceeding the pre-pandemic level of 7.49 visits per person-year in 2019 (adjusted percent change = 5.1%; 95% CI 0.6% to 9.9%); inpatient and ED visits returned to pre-pandemic levels, 0.103 and 0.275 visits per person-year respectively among all members, although they remained 7.5% and 8.0% lower than pre-pandemic levels among members without a documented history of COVID-19. Telehealth visits, which were approximately 42% of the volume of outpatient visits during the later pandemic period, were increased by 97.5% (95% CI 86.0% to 109.7%) from 0.865 visits per person-year in 2019 to 2.35 visits per person-year in the later pandemic period. The trends in KPSC were like those of the entire study population. Visit rates from January 2022 to June 2023 were stable and appeared to be a continuation of the utilization levels observed at the end of 2021. CONCLUSIONS: Telehealth services became a mainstay of the health care system during the late COVID-19 pandemic period. Inpatient and ED visits returned to pre-pandemic levels, although they remained low among members without evidence of COVID-19. Our findings provide valuable information for longer-term strategic resource allocation for patient care in the post-pandemic period and for designing observational studies involving the pandemic period. |
Lack of evidence for vaccine-associated enhanced disease from COVID-19 vaccines among adults in the Vaccine Safety Datalink
Boyce TG , McClure DL , Hanson KE , Daley MF , DeSilva MB , Irving SA , Jackson LA , Klein NP , Lewin B , Williams JTB , Duffy J , McNeil MM , Weintraub ES , Belongia EA . Pharmacoepidemiol Drug Saf 2024 33 (8) e5863 PURPOSE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19). METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect. RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness. CONCLUSION: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED. |
Sporozoite immunization: Innovative Translational Science to Support the Fight against malaria
Richie TL , Church LWP , Murshedkar T , Billingsley PF , James ER , Chen MC , Abebe Y , Natasha Kc , Chakravarty S , Dolberg D , Healy SA , Diawara H , Sissoko MS , Sagara I , Cook DM , Epstein JE , Mordmüller B , Kapulu M , Kreidenweiss A , Franke-Fayard B , Agnandji ST , López Mikue MA , McCall MBB , Steinhardt L , Oneko M , Olotu A , Vaughan AM , Kublin JG , Murphy SC , Jongo S , Tanner M , Sirima SB , Laurens MB , Daubenberger C , Silva JC , Lyke KE , Janse CJ , Roestenberg M , Sauerwein RW , Abdulla S , Dicko A , Kappe SHI , Sim BKL , Duffy PE , Kremsner PG , Hoffman SL . Expert Rev Vaccines 2023 22 (1) 964-1007 INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives. |
Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) Using Natural Language Processing (preprint)
Zheng C , Duffy J , Liu IA , Sy LS , Navarro RA , Kim SS , Ryan DS , Chen W , Qian L , Mercado C , Jacobsen SJ . medRxiv 2021 2021.05.05.21256555 Background Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, there is a lack of population-based studies due to the challenge of identifying SIRVA cases in large health care databases.Objective To develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes.Methods We conducted the study among members of a large integrated health care organization who were vaccinated between 04/1/2016 and 12/31/2017 and had subsequent diagnosis codes indicative of shoulder injury. Based on a training dataset with a chart review reference standard of 164 individuals, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified three groups of positive SIRVA cases (definite, probable and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated individuals. We then applied the final automated NLP algorithm to a broader cohort of vaccinated individuals with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases.Results In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 individuals without SIRVA. In the broader cohort of 53,585 individuals, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.3%, 67.7% and 18.9%, respectively.Conclusions The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.Competing Interest StatementLina Sy received research support from GlaxoSmithKline, Dynavax, Seqirus, and Novavax for studies unrelated to this paper. All other authors report no conflicts of interest related to the submitted work.Funding StatementThis study was funded through the Vaccine Safety Datalink under contract 200-2012-53580 from the Centers for Disease Control and Prevention (CDC). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Institutional Review Board at KPSC approved this study.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated and/or analyzed during the current study are not publicly available due to ethical standards. The authors do not have permission to share data.CIconfidence intervalEHRelectronic health recordsICD-10-CMInternational Classification of Diseases 10th Revision Clinical ModificationKPSCKaiser Permanente Southern CaliforniaNLPnatural language processingNPVnegative predictive valuePPVpos tive predictive valueSIRVAshoulder injury related to vaccine administrationVICPNational Vaccine Injury Compensation Program |
Distinct origins and transmission pathways of bla(KPC) enterobacterales across three U.S. States
Lapp Z , Octaria R , O'Malley SM , Nguyen TN , Wolford H , Crawford R , Moore C , Snippes Vagnone P , Noel D , Duffy N , Pirani A , Thomas LS , Pattee B , Pearson C , Bulens SN , Hoffman S , Kainer M , Anacker M , Meek J , See I , Gontjes KJ , Chan A , Lynfield R , Maloney M , Hayden MK , Snitkin E , Slayton RB . J Clin Microbiol 2023 61 (8) e0025923 Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla(KPC)-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla(KPC)-carrying Klebsiella pneumoniae ST258, and clonal expansion of bla(KPC)-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla(KPC)-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of bla(KPC) plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions. |
Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink
Katherine Yih W , Daley MF , Duffy J , Fireman B , McClure DL , Nelson JC , Qian L , Smith N , Vazquez-Benitez G , Weintraub E , Williams JTB , Xu S , Maro JC . Vaccine 2023 41 (36) 5265-5270 BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree." |
Population estimates of HIV risk factors to inform HIV prevention programming for adolescent girls and young women
Howard AL , Chiang L , Picchetti V , Zhu L , Hegle J , Patel P , Saul J , Wasula L , Nantume S , Coomer R , Kamuingona R , Oluoch RP , Mharadze T , Duffy M , Kambona CA , Ramphalla P , Fathim KM , Massetti GM . AIDS Educ Prev 2023 35 20-38 Violence Against Children and Youth Survey (VACS) data from seven countries were analyzed to estimate population-level eligibility for the President's Emergency Plan for AIDS Relief (PEPFAR) Determined, Resilient, Empowered, AIDS-Free, Mentored, and Safe (DREAMS) HIV prevention program for adolescent girls and young women (AGYW). The prevalence of overall eligibility and individual risk factors, including experiences of violence, social, and behavioral risks differ across countries and age groups. A large proportion of AGYW across all countries and age groups examined have at least one risk factor making them eligible for DREAMS. Experiencing multiple risks is also common, suggesting that researchers and programs could work together to identify combinations of risk factors that put AGYW at greatest risk of HIV acquisition, or that explain most new HIV infections, to more precisely target the most vulnerable AGYW. The VACS provides important data for such analyses to refine DREAMS and other youth programming. |
Understanding gender-based violence service delivery in CDC-supported health facilities: 15 Sub-Saharan African Countries, 2017-2021
Kanagasabai U , Valleau C , Cain M , Chevalier MS , Hegle J , Patel P , Benevides R , Trika JB , Angumua C , Mpingulu M , Ferdinand K , Sida F , Galloway K , Kambona C , Oluoch P , Msungama W , Katengeza H , Correia D , Duffy M , Cossa RMV , Coomer R , Ayo A , Ukanwa C , Tuyishime E , Dladla S , Drummond J , Magesa D , Kitalile J , Apondi R , Okuku J , Chisenga T , Cham HJ . AIDS Educ Prev 2023 35 39-51 Gender-based violence (GBV) is a complex issue deeply rooted in social structures, making its eradication challenging. GBV increases the risk of HIV transmission and is a barrier to HIV testing, care, and treatment. Quality clinical services for GBV, which includes the provision of HIV postexposure prophylaxis (PEP), vary, and service delivery data are lacking. We describe GBV clinical service delivery in 15 countries supported by the President's Emergency Plan for AIDS Relief (PEPFAR) through the U.S. Centers for Disease Control and Prevention. Through a descriptive statistical analysis of PEPFAR Monitoring, Evaluation, and Reporting (MER) data, we found a 252% increase in individuals receiving GBV clinical services, from 158,691 in 2017 to 558,251 in 2021. PEP completion was lowest (15%) among 15-19-year-olds. Understanding GBV service delivery is important for policy makers, program managers, and providers to guide interventions to improve the quality of service delivery and contribute to HIV epidemic control. |
Validating Wave 1 (2014) urinary cotinine and TNE-2 cut-points for differentiating Wave 4 (2017) cigarette use from non-use in the US using data from the PATH Study
Edwards KC , Khan A , Sharma E , Wang L , Feng J , Blount BC , Sosnoff CS , Smith DM , Goniewicz ML , Pearson J , Villanti AC , Delnevo CD , Bover Manderski MT , Hatsukami DK , Niaura R , Everard C , Kimmel HL , Duffy K , Rostron BL , Del Valle-Pinero AY , van Bemmel DM , Stanton CA , Hyland A . Cancer Epidemiol Biomarkers Prev 2023 32 (9) 1233-1241 BACKGROUND: Sex and racial/ethnic identity specific cut-points for validating tobacco use using Wave 1 (W1) of the PATH Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and Total Nicotine Equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use. METHODS: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. Receiver Operating Characteristic curves were used to determine the optimal W4 cut-points to distinguish P30D users from non-users, and evaluate if the cut-points significantly differed from W1. RESULTS: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7- 4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1 derived cut-points (e.g., W1 exclusive= 40.5 ng/mL cotinine [95% CI: 26.1-62.8], W4 exclusive = 29.9 ng/ml cotinine [95% CI: 13.5-66.4]), among most demographic subgroups. CONCLUSION: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4. IMPACT: Findings from can be used in clinical and epidemiological studies to reduce misclassification of cigarette smoking status. |
Four principles to establish a universal virus taxonomy.
Simmonds P , Adriaenssens EM , Zerbini FM , Abrescia NGA , Aiewsakun P , Alfenas-Zerbini P , Bao Y , Barylski J , Drosten C , Duffy S , Duprex WP , Dutilh BE , Elena SF , García ML , Junglen S , Katzourakis A , Koonin EV , Krupovic M , Kuhn JH , Lambert AJ , Lefkowitz EJ , Łobocka M , Lood C , Mahony J , Meier-Kolthoff JP , Mushegian AR , Oksanen HM , Poranen MM , Reyes-Muñoz A , Robertson DL , Roux S , Rubino L , Sabanadzovic S , Siddell S , Skern T , Smith DB , Sullivan MB , Suzuki N , Turner D , Van Doorslaer K , Vandamme AM , Varsani A , Vasilakis N . PLoS Biol 2023 21 (2) e3001922 A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., "arboviruses"), infecting a certain type of host (e.g., "mycoviruses," "bacteriophages") or displaying specific pathogenicity (e.g., "human immunodeficiency viruses"), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent. |
A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink.
Yih WK , Daley MF , Duffy J , Fireman B , McClure D , Nelson J , Qian L , Smith N , Vazquez-Benitez G , Weintraub E , Williams JTB , Xu S , Maro JC . Vaccine 2022 BACKGROUND: Except for spontaneous reporting systems, vaccine safety monitoring generally involves pre-specifying health outcomes and post-vaccination risk windows of concern. Instead, we used tree-based data-mining to look more broadly for possible adverse events after Pfizer-BioNTech, Moderna, and Janssen COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees receiving1 dose of COVID-19 vaccine in 2020-2021 were followed for 70days after Pfizer-BioNTech or Moderna and 56days after Janssen vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the post-vaccination follow-up period. We used the self-controlled tree-temporal scan statistic and TreeScan software. Monte Carlo simulation was used to estimate p-values; p=0.01 was the pre-specified cut-off for statistical significance of a cluster. RESULTS: There were 4.1, 2.6, and 0.4 million Pfizer-BioNTech, Moderna, and Janssen vaccinees, respectively. Clusters after Pfizer-BioNTech vaccination included: (1) unspecified adverse effects, (2) common vaccine reactions, such as fever, myalgia, and headache, (3) myocarditis/pericarditis, and (4) less specific cardiac or respiratory symptoms, all with the strongest clusters generally after Dose 2; and (5) COVID-19/viral pneumonia/sepsis/respiratory failure in the first 3weeks after Dose 1. Moderna results were similar but without a significant myocarditis/pericarditis cluster. Further investigation suggested the fifth signal group was a manifestation of mRNA vaccine effectiveness after the first 3weeks. Janssen vaccinees had clusters of unspecified or common vaccine reactions, gait/mobility abnormalities, and muscle weakness. The latter two were deemed to have arisen from confounding related to practices at one site. CONCLUSIONS: We detected post-vaccination clusters of unspecified adverse effects, common vaccine reactions, and, for the mRNA vaccines, chest pain and palpitations, as well as myocarditis/pericarditis after Pfizer-BioNTech Dose 2. Unique advantages of this data mining are its untargeted nature and its inherent adjustment for the multiplicity of diagnoses and risk intervals scanned. |
Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink.
Katherine Yih W , Daley MF , Duffy J , Fireman B , McClure D , Nelson J , Qian L , Smith N , Vazquez-Benitez G , Weintraub E , Williams JTB , Xu S , Maro JC . Vaccine 2022 41 (2) 460-466 BACKGROUND: The Centers for Disease Control and Prevention's Vaccine Safety Datalink (VSD) has been performing safety surveillance for COVID-19 vaccines since their earliest authorization in the United States. Complementing its real-time surveillance for pre-specified health outcomes using pre-specified risk intervals, the VSD conducts tree-based data-mining to look for clustering of a broad range of health outcomes after COVID-19 vaccination. This study's objective was to use this untargeted, hypothesis-generating approach to assess the safety of first booster doses of Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Ad26.COV2.S) COVID-19 vaccines. METHODS: VSD enrollees receiving a first booster of COVID-19 vaccine through April 2, 2022 were followed for 56 days. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within both the hierarchical ICD-10-CM code structure and the follow-up period. The self-controlled tree-temporal scan statistic was used, conditioning on the total number of cases for each diagnosis. P-values were estimated by Monte Carlo simulation; p = 0.01 was pre-specified as the cut-off for statistical significance of clusters. RESULTS: More than 2.4 and 1.8 million subjects received Pfizer-BioNTech and Moderna boosters after an mRNA primary series, respectively. Clusters of urticaria/allergy/rash were found during Days 10-15 after the Moderna booster (p = 0.0001). Other outcomes that clustered after mRNA boosters, mostly with p = 0.0001, included unspecified adverse effects, common vaccine-associated reactions like fever and myalgia, and COVID-19. COVID-19 clusters were in Days 1-10 after booster receipt, before boosters would have become effective. There were no noteworthy clusters after boosters following primary Janssen vaccination. CONCLUSIONS: In this untargeted data-mining study of COVID-19 booster vaccination, a cluster of delayed-onset urticaria/allergy/rash was detected after the Moderna booster, as has been reported after Moderna vaccination previously. Other clusters after mRNA boosters were of unspecified or common adverse effects and COVID-19, the latter evidently reflecting immunity to COVID-19 after 10 days. |
Safety monitoring of JYNNEOS Vaccine during the 2022 Mpox outbreak - United States, May 22-October 21, 2022
Duffy J , Marquez P , Moro P , Weintraub E , Yu Y , Boersma P , Donahue JG , Glanz JM , Goddard K , Hambidge SJ , Lewin B , Lewis N , Rouse D , Shimabukuro T . MMWR Morb Mortal Wkly Rep 2022 71 (49) 1555-1559 JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) is recommended in the United States for persons exposed to or at high risk for exposure to Monkeypox virus during the 2022 monkeypox (mpox) outbreak (1). JYNNEOS is a live, nonreplicating viral vaccine licensed for the prevention of smallpox and mpox in adults aged ≥18 years, administered as a 0.5-mL 2-dose series given 28 days apart by subcutaneous injection (2). On August 9, 2022, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for administration of 0.1 mL doses by intradermal injection for adults aged ≥18 years as a strategy to increase vaccine supply, and administration of 0.5 mL doses subcutaneously for persons aged <18 years (3). During May 22-October 21, 2022, a total of 987,294 JYNNEOS vaccine doses were administered in the United States. CDC has monitored JYNNEOS vaccine safety using the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD) for vaccine recipients of all ages, and through single-patient emergency Investigational New Drug (EIND) procedures for persons aged <18 years vaccinated before August 9, 2022. The most common adverse health events reported to VAERS for adults were nonserious and included injection site reactions, which was consistent with the prelicensure studies. Adverse health events were reported at similar rates for doses received by intradermal and subcutaneous administration. Serious adverse events were rare in adults, and no serious adverse events have been identified among persons aged <18 years. Overall, postlicensure and postauthorization surveillance to date support JYNNEOS vaccine safety. |
Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy
Kc N , Church LWP , Riyahi P , Chakravarty S , Seder RA , Epstein JE , Lyke KE , Mordmüller B , Kremsner PG , Sissoko MS , Healy S , Duffy PE , Jongo SA , Nchama Vunn , Abdulla S , Mpina M , Sirima SB , Laurens MB , Steinhardt LC , Oneko M , Li M , Murshedkar T , Billingsley PF , Sim BKL , Richie TL , Hoffman SL . Front Immunol 2022 13 1006716 BACKGROUND: While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination. METHODS: Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa). RESULTS: Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females. CONCLUSION: Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver. |
Association between aluminum exposure from vaccines before age 24 months and persistent asthma at age 24 to 59 months
Daley MF , Reifler LM , Glanz JM , Hambidge SJ , Getahun D , Irving SA , Nordin JD , McClure DL , Klein NP , Jackson ML , Kamidani S , Duffy J , DeStefano F . Acad Pediatr 2022 23 (1) 37-46 OBJECTIVE: To assess the association between cumulative aluminum exposure from vaccines before age 24 months and persistent asthma at age 24 to 59 months. METHODS: A retrospective cohort study was conducted in the Vaccine Safety Datalink (VSD). Vaccination histories were used to calculate cumulative vaccine-associated aluminum in milligrams (mg). The persistent asthma definition required one inpatient or 2 outpatient asthma encounters, and 2 long-term asthma control medication dispenses. Cox proportional hazard models were used to evaluate the association between aluminum exposure and asthma incidence, stratified by eczema presence/absence. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) per 1 mg increase in aluminum exposure were calculated, adjusted for birth month/year, sex, race/ethnicity, VSD site, prematurity, medical complexity, food allergy, severe bronchiolitis, and health care utilization. RESULTS: The cohort comprised 326,991 children, among whom 14,337 (4.4%) had eczema. For children with and without eczema, the mean (standard deviation [SD]) vaccine-associated aluminumexposure was4.07mg (SD0.60) and 3.98mg (SD0.72), respectively. Among children with and without eczema, 6.0% and 2.1%, respectively, developed persistent asthma. Among children with eczema, vaccine-associated aluminum was positively associated with persistent asthma (aHR 1.26 per 1 mg increase in aluminum, 95% CI 1.07, 1.49); a positive association was also detected among children without eczema (aHR 1.19, 95% CI 1.14, 1.25). CONCLUSION: In a large observational study, a positive association was found between vaccine-related aluminum exposure and persistent asthma. While recognizing the small effect sizes identified and the potential for residual confounding, additional investigation of this hypothesis appears warranted. |
Active post-licensure safety surveillance for recombinant zoster vaccine using electronic health record data
Nelson JC , Ulloa-Prez E , Yu O , Cook AJ , Jackson ML , Belongia EA , Daley MF , Harpaz R , Kharbanda EO , Klein NP , Naleway AL , Tseng HF , Weintraub ES , Duffy J , Yih WK , Jackson LA . Am J Epidemiol 2022 192 (2) 205-216 Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster and its complications in older adults. In this prospective, post-licensure Vaccine Safety Datalink (VSD) study using electronic health records, we sequentially monitored a real-world population of adults aged 50 years and older who received care at multiple VSD health systems in the United States to identify potential increased risks of 10 pre-specified priority outcomes, including stroke, anaphylaxis, and Guillain-Barr Syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative either to historical (2013-2017) recipients of Zoster Vaccine Live (ZVL), a live-attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccinated persons who had an annual well-visit during the 2018-2019 study period. We confirmed pre-licensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed. |
Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) in the United States: Development and Validation of a Natural Language Processing Method.
Zheng C , Duffy J , Liu IA , Sy LS , Navarro RA , Kim SS , Ryan DS , Chen W , Qian L , Mercado C , Jacobsen SJ . JMIR Public Health Surveill 2022 8 (5) e30426 BACKGROUND: Shoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, due to the difficulty of finding SIRVA cases in large health care databases, population-based studies are scarce. OBJECTIVE: The goal of the research was to develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes. METHODS: We conducted the study among members of a large integrated health care organization who were vaccinated between April 1, 2016, and December 31, 2017, and had subsequent diagnosis codes indicative of shoulder injury. Based on a training data set with a chart review reference standard of 164 cases, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified 3 groups of positive SIRVA cases (definite, probable, and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated cases. We then applied the final automated NLP algorithm to a broader cohort of vaccinated persons with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases. RESULTS: In the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 cases without SIRVA. In the broader cohort of 53,585 vaccinations, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.5% (278/291), 67.7% (84/124), and 17.3% (9/52), respectively. CONCLUSIONS: The algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation. |
Changes in incidence rates of outcomes of interest in vaccine safety studies during the COVID-19 pandemic.
Xu S , Hong V , Sy LS , Glenn SC , Ryan DS , Morrissette KL , Nelson JC , Hambidge SJ , Crane B , Zerbo O , DeSilva MB , Glanz JM , Donahue JG , Liles E , Duffy J , Qian L . Vaccine 2022 40 (23) 3150-3158 BACKGROUND: The COVID-19 pandemic caused an abrupt drop in in-person health care (inpatient, Emergency Department, outpatient) and an increase in telehealth care, which poses challenges in vaccine safety studies that identify outcomes from in-person encounters. We examined the changes in incidence rates of selected encounter-based outcomes during the COVID-19 pandemic. METHODS: We assembled a cohort of members from 8 Vaccine Safety Datalink sites from January 1, 2017 through December 31, 2020. Using ICD-10 diagnosis codes or laboratory criteria, we identified 21 incident outcomes in traditional in-person settings and all settings. We defined 4 periods in 2020: January-February (pre-pandemic), April-June (early pandemic), July-September (middle pandemic), and October-December (late pandemic). We defined four corresponding periods in each year during 2017-2019. We calculated incidence rates, conducted difference in difference (DiD) analyses, and reported ratios of incidence rate ratios (RRR) to examine changes in rates from pre-pandemic to early, middle, and late pandemic in 2020, after adjusting for changes across similar periods in 2017-2019. RESULTS: Among>10 million members, regardless of setting and after adjusting for changes during 2017-2019, we found that incidence rates of acute disseminated encephalomyelitis, encephalitis/myelitis/encephalomyelitis/meningoencephalitis, and thrombotic thrombocytopenic purpura did not significantly change from the pre-pandemic to early, middle or late pandemic periods (p-values0.05). Incidence rates decreased from the pre-pandemic to early pandemic period during 2020 for acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, convulsions/seizures, Guillain-Barr syndrome, immune thrombocytopenia (ITP), narcolepsy/cataplexy, hemorrhagic stroke, ischemic stroke, and venous thromboembolism (p-values<0.05). Incidence rates of Bell's palsy, ITP, and narcolepsy/cataplexy were higher in all settings than in traditional in-person settings during the three pandemic periods (p-values<0.05). CONCLUSION: Rates of some clinical outcomes during the pandemic changed and should not be used as historical background rates in vaccine safety studies. Inclusion of telehealth visits should be considered for vaccine studies involving Bell's palsy, ITP, and narcolepsy/cataplexy. |
Risk factors for Ebola virus disease among household care providers, Sierra Leone, 2015
Duffy N , Bruden D , Thomas H , Nichols E , Knust B , Hennessy T , Reichler MR . Int J Epidemiol 2022 51 (5) 1457-1468 BACKGROUND: Household contacts who provide care to an Ebola virus disease (EVD) case have a 3-fold higher risk of EVD compared with contacts who do not provide care. METHODS: We enrolled persons with confirmed EVD from December 2014 to April 2015 in Freetown, Sierra Leone, and their household contacts. Index cases and contacts were interviewed, and contacts were followed for 21 days to identify secondary cases. Epidemiological data were analysed to describe household care and to identify risk factors for developing EVD. RESULTS: Of 838 contacts in 147 households, 156 (17%) self-reported providing care to the index case; 56 households had no care provider, 52 a single care provider and 39 multiple care providers. The median care provider age was 29 years, 68% were female and 32% were the index case's spouse. Care providers were more likely to report physical contact, contact with body fluids or sharing clothing, bed linens or utensils with an index case, compared with non-care providers (P <0.01). EVD risk among non-care providers was greater when the number of care providers in the household increased (odds ratio: 1.61; 95% confidence interval: 1.1, 2.4). In multivariable analysis, factors associated with care provider EVD risk included no piped water access and absence of index case fever, and protective factors included age <20 years and avoiding the index case. CONCLUSIONS: Limiting the number of care providers in a household could reduce the risk of EVD transmission to both care providers and non-care providers. Strategies to protect care providers from EVD exposure are needed. |
Investigation of A SARS-CoV-2 Delta (B.1.617.2) Variant Outbreak Among Residents of a Skilled Nursing Facility and Vaccine Effectiveness Analysis - Maricopa County, Arizona, June-July 2021.
Dale AP , Almendares O , Howard B , Burnett E , Prasai S , Arons M , Collins J , Duffy N , Pandit U , Brady S , White J , Garrett B , Kirking HL , Sunenshine R , Tate JE , Scott SE . Clin Infect Dis 2022 75 (1) e20-e26 BACKGROUND: Short-term rehabilitation units present unique infection control challenges due to high turnover and medically complex residents. In June 2021, Maricopa County Department of Public Health (MCDPH) was notified of a SARS-CoV-2 Delta outbreak in a skilled nursing facility short-term rehabilitation unit. We describe the outbreak and assess vaccine effectiveness (VE). METHODS: Facility electronic medical records were reviewed for residents who spent >1 night on the affected unit between June 10-July 23, 2021, to collect demographics, SARS-CoV-2 test results, underlying medical conditions, vaccination status, and clinical outcomes. COVID-19 VE estimates using Cox proportional hazards models were calculated. RESULTS: Forty (37%) of 109 short-stay rehabilitation unit residents who met inclusion criteria tested positive for SARS-CoV-2. SARS-CoV-2 positive case-patients were mostly male (58%) and white (78%) with a median age of 65 (range: 27-92) years; 11 (27%) were immunocompromised. Of residents, 39% (10 cases; 32 non-cases) received 2-doses and 9% (4 cases, 6 non-cases) received 1-dose of mRNA vaccine. Among non-immunocompromised residents, adjusted 2-dose primary-series mRNA VE against symptomatic infection was 80% (95% CI: 15, 95). More cases were hospitalized (33%) or died (38%) than non-cases (10% hospitalized; 16% died). CONCLUSIONS: In this large SARS-CoV-2 Delta outbreak in a high-turnover short term rehabilitation unit, a low vaccination rate and medically complex resident population were noted alongside severe outcomes. VE of 2-dose primary-series mRNA vaccine against symptomatic infection was the highest in non-immunocompromised residents. Health departments can use vaccine coverage data to prioritize facilities for assistance in preventing outbreaks. |
Risk for Shoulder Conditions After Vaccination: A Population-Based Study Using Real-World Data.
Zheng C , Duffy J , Liu IA , Sy LS , Chen W , Qian L , Navarro RA , Ryan DS , Kim SS , Mercado C , Jacobsen SJ . Ann Intern Med 2022 175 (5) 634-643 BACKGROUND: Although shoulder conditions have been reported as an adverse event after intramuscular vaccination in the deltoid muscle, epidemiologic data on shoulder conditions after vaccination are limited. OBJECTIVE: To estimate the risk for shoulder conditions after vaccination and assess possible risk factors. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Southern California, a large integrated health care organization. PARTICIPANTS: Kaiser Permanente Southern California members aged 3 years or older who had an intramuscular vaccination administered in the deltoid muscle between 1 April 2016 and 31 December 2017. MEASUREMENTS: A natural language processing (NLP) algorithm was used to identify potential shoulder conditions among vaccinated persons with shoulder disorder diagnosis codes. All NLP-identified cases were manually chart confirmed on the basis of our case definition. The characteristics of vaccinated persons with and without shoulder conditions were compared. RESULTS: Among 3 758 764 administered vaccinations, 371 cases of shoulder condition were identified, with an estimated incidence of 0.99 (95% CI, 0.89 to 1.09) per 10 000 vaccinations. The incidence was 1.22 (CI, 1.10 to 1.35) for the adult (aged ≥18 years) and 0.05 (CI, 0.02 to 0.14) for the pediatric (aged 3 to 17 years) vaccinated populations. In the adult vaccinated population, advanced age, female sex, an increased number of outpatient visits in the 6 months before vaccination, lower Charlson Comorbidity Index, and pneumococcal conjugate vaccine were associated with a higher risk for shoulder conditions. Among influenza vaccines, quadrivalent vaccines were associated with an increased risk for shoulder conditions. Simultaneous administration of vaccines was associated with a higher risk for shoulder conditions among elderly persons. LIMITATION: Generalizability to other health care settings, use of administrative data, and residual confounding. CONCLUSION: These population-based data suggest a small absolute risk for shoulder conditions after vaccination. Given the high burden of shoulder conditions, clinicians should pay attention to any factors that may further increase risks. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention. |
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